The basic objective of this research is to improve the radiotherapy of brain tumors. For a given dose, the radiation-induced DNA damage appears to be identical both in dividing and nondividing cells; however, the DNA repair kinetics of these two cell types are different. Therefore, determination of the DNA repair kinetics in brain tumor and normal brain cells both in vitro and in vivo should lead to a radiation treatment schedule which will maximize the accumulation of unrepaired DNA damage in brain tumor cells while minimizing the accumulation of unrepaired DNA damage in normal nondividing brain cells. Modifications of the McGrath and Williams alkaline sucrose gradient ultracentrifugation technique which yield large DNA-containing species (greater than 500S) from unirradiated cells in both swinging-bucket and zonal rotors will be used to determine the DNA damage and repair kinetics of both the tumor and normal brain cells associated with the Fischer rat glioma #9 intracerebral tumor model. The research protocol is as follows: 1) To determine in vitro and in vivo the DNA damage and repair kinetics of rat 9L tumor cells after single and split doses of ionizing radiation; 2) To determine in vivo the DNA damage and repiar kinetics of normal nondividing rat brain cells after single and split doses of ionizing radiation; and 3) To evaluate radiation treatment schedules derived from the above investigations by measuring simultaneously in the same rat, the in vivo state of the genetic material in both the tumor and normal brain cells. Because the work will be done in vivo where all of the perturbations imposed by the in toto physiological response of the animal to the treatment schedule are included, the final results should be directly relevant to the problems encountered in the clinical treatment of brain tumors.